tbuckley/cabot-search huggingface dataset:
STE20 kinase TAOK3 regulates type 2 immunity and metabolism in obesity
Authors: Bastiaan Maes, Farzaneh Fayazpour, Leen Catrysse, Guillaume Lornet, Evelien Van De Velde, Caroline De Wolf, Sofie De Prijck, Justine Van Moorleghem, Manon Vanheerswynghels, Kim Deswarte, Benedicte Descamps, Christian Vanhove, Bart Van der Schueren, Roman Vangoitsenhoven, Hamida Hammad, Sophie Janssens, Bart N. Lambrecht
Journal: The Journal of Experimental Medicine (2023)

Healthy adipose tissue (AT) contains ST2+ Tregs, ILC2s, and alternatively activated macrophages that are lost in mice or humans on high caloric diet. Understanding how this form of type 2 immunity is regulated could improve treatment of obesity. The STE20 kinase Thousand And One amino acid Kinase-3 (TAOK3) has been linked to obesity in mice and humans, but its precise function is unknown. We found that ST2+ Tregs are upregulated in visceral epididymal white AT (eWAT) of Taok3−/− mice, dependent on IL-33 and the kinase activity of TAOK3. Upon high fat diet feeding, metabolic dysfunction was attenuated in Taok3−/− mice. ST2+ Tregs disappeared from eWAT in obese wild-type mice, but this was not the case in Taok3−/− mice. Mechanistically, AT Taok3−/− Tregs were intrinsically more responsive to IL-33, through higher expression of ST2, and expressed more PPARγ and type 2 cytokines. Thus, TAOK3 inhibits adipose tissue Tregs and regulates immunometabolism under excessive caloric intake.
Radiation dose, schedule, and novel systemic targets for radio-immunotherapy combinations
Authors: Lilit Karapetyan, Uzoma K Iheagwara, Adam C Olson, Steven J Chmura, Heath K Skinner, Jason J Luke
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Immunotherapy combinations are being investigated to expand the benefit of immune checkpoint blockade across many cancer types. Radiation combinations, in particular using stereotactic body radiotherapy, are of keen interest because of underlying mechanistic rationale, safety, and availability as a standard of care in certain cancers. In addition to direct tumor cytotoxicity, radiation therapy has immunomodulatory effects such as induction of immunogenic cell death, enhancement of antigen presentation, and expansion of the T-cell receptor repertoire as well as recruitment and increased activity of tumor-specific effector CD8+ cells. Combinations of radiation with cytokines and/or chemokines and anti-programmed death 1 and anticytotoxic T-lymphocyte antigen 4 therapies have demonstrated safety and feasibility, as well as the potential to improve long-term outcomes and possibly induce out of irradiated field or abscopal responses. Novel immunoradiotherapy combinations represent a promising therapeutic approach to overcome radioresistance and further enhance systemic immunotherapy. Potential benefits include reversing CD8+ T-cell exhaustion, inhibiting myeloid-derived suppressor cells, and reversing M2 macrophage polarization as well as decreasing levels of colony-stimulating factor-1 and transforming growth factor-β. Here, we discuss current data and mechanistic rationale for combining novel immunotherapy agents with radiation therapy.
Covid-19 inquiry: Experts clash with political leaders over effects of austerity
Authors: Gareth Iacobucci
Journal: BMJ (2023)

Covid-19 inquiry: Experts with political leaders over effects of austerityThis week the UK's covid-19 public inquiry kicked into gear, hearing evidence from high profile witnesses.Gareth Iacobucci summarises the key developments Gareth IacobucciExperts and medical leaders have heavily criticised the former UK prime minister David Cameron and his chancellor George Osborne after they denied that the austerity programme they implemented while in government had any adverse effects on the UK's preparedness for the covid-19 pandemic.Between 19 and 21 June the inquiry heard evidence from Cameron and Osborne, who were prime minister and chancellor from 2010 to 2016, along with Jeremy Hunt, the current chancellor, who served as England's health and social care secretary between 2012
Inclusivity in Research Matters: Variants in <i>PVT1</i> Specific to Persons of African Descent Are Associated with Pulmonary Fibrosis
Authors: Lori Garman, Nathan Pezant, Bryan A. Dawkins, Astrid Rasmussen, Albert M. Levin, Benjamin A. Rybicki, Michael C. Iannuzzi, Harini Bagavant, Umesh S. Deshmukh, Courtney G. Montgomery
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Inclusivity in Research Matters: Variants in PVT1 Specific to Persons of African Descent Are Associated with Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 209(1), pp. 106–109
Underwater cap-suction pseudopolyp formation for endoscopic mucosal resection: a simple technique for treating flat, appendiceal orifice or ileocecal valve colorectal lesions
Authors: Hugo Uchima, Anna Calm, Raquel Muñoz-González, Noemí Caballero, Mercé Rosinach, Ingrid Marín, Juan Colán-Hernández, Ignacio Iborra, Edgar Castillo-Regalado, Rocío Temiño, Alfredo Mata, Román Turró, Jorge Espinós, Vicente Moreno De Vega, Maria Pellisé
Journal: Endoscopy (2023)

We aimed to evaluate the safety and technical success of an easy-to-use technique that applies underwater cap suction pseudopolyp formation to facilitate the resection of flat lesions or those at the appendiceal orifice or ileocecal valve.We retrospectively analyzed a register of consecutive cap suction underwater endoscopic mucosal resection (CAP-UEMR) procedures performed at two centers between September 2020 and December 2021. Procedures were performed using a cone-shaped cap, extending 7 mm from the endoscope tip, to suction the lesion while submerged underwater, followed by underwater snare resection. Our primary end point was technical success, defined as macroscopic complete resection.We treated 83 lesions (median size 20 mm; interquartile range [IQR] 15-30 mm) with CAP-UEMR: 64 depressed or flat lesions (18 previously manipulated, 9 with difficult access), 11 from the appendix, and 8 from the ileocecal valve. Technical success was 100 %. There were seven intraprocedural bleedings and two delayed bleedings, all managed endoscopically. No perforations or other complications occurred. Among the 64 lesions with follow-up colonoscopy, only one recurrence was detected, which was treated endoscopically.CAP-UEMR was a safe and effective technique for removing nonpolypoid colorectal lesions, including those arising from the appendiceal orifice or ileocecal valve.
Reply to Ward <i>et al.</i>
Authors: Micheál Mac Aogáin, Jayanth Kumar Narayana, Sanjay H. Chotirmall
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: The Potential Role of Gastric Microbiology in Respiratory Disease." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
The Potential Role of Gastric Microbiology in Respiratory Disease
Authors: Chris Ward, Hafez Al Momani, Melissa J. McDonnell, Desmond M. Murphy, Laura Walsh, John Mac Sharry, Mike Griffin, Ian A. Forrest, Rhys Jones, Amaran Krishnan, Jeffrey Pearson, Robert M. Rutherford
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"The Potential Role of Gastric Microbiology in Respiratory Disease." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
MCL1 regulates AML cells metabolism via direct interaction with HK2. Metabolic signature at onset predicts overall survival in AMLs’ patients
Authors: Gianfranco Catalano, Alessandra Zaza, Cristina Banella, Elvira Pelosi, Germana Castelli, Elisabetta de Marinis, Ariela Smigliani, Serena Travaglini, Tiziana Ottone, Mariadomenica Divona, Maria Ilaria Del Principe, Francesco Buccisano, Luca Maurillo, Emanuele Ammatuna, Ugo Testa, Clara Nervi, Adriano Venditti, Maria Teresa Voso, Nelida Ines Noguera
Journal: Leukemia (2023)
Rapid and stain-free quantification of viral plaque via lens-free holography and deep learning
Authors: Tairan Liu, Yuzhu Li, Hatice Ceylan Koydemir, Yijie Zhang, Ethan Yang, Merve Eryilmaz, Hongda Wang, Jingxi Li, Bijie Bai, Guangdong Ma, Aydogan Ozcan
Journal: Nature Biomedical Engineering (2023)

We present a rapid and stain-free quantitative viral plaque assay using lensfree holographic imaging and deep learning. This cost-effective, compact, and automated device significantly reduces the incubation time needed for traditional plaque assays while preserving their advantages over other virus quantification methods. This device captures ~0.32 Giga-pixel/hour phase information of the objects per test well, covering an area of ~30x30 mm^2, in a label-free manner, eliminating staining entirely. We demonstrated the success of this computational method using vesicular stomatitis virus (VSV), herpes simplex virus (HSV-1) and encephalomyocarditis virus (EMCV). Using a neural network, this stain-free device automatically detected the first cell lysing events due to the VSV viral replication as early as 5 hours after the incubation, and achieved >90% detection rate for the VSV plaque-forming units (PFUs) with 100% specificity in <20 hours, providing major time savings compared to the traditional plaque assays that take at least 48 hours. Similarly, this stain-free device reduced the needed incubation time by ~48 hours for HSV-1 and ~20 hours for EMCV, achieving >90% detection rate with 100% specificity. We also demonstrated that this data-driven plaque assay offers the capability of quantifying the infected area of the cell monolayer, performing automated counting and quantification of PFUs and virus-infected areas over a 10-fold larger dynamic range of virus concentration than standard viral plaque assays. This compact, low-cost, automated PFU quantification device can be broadly used in virology research, vaccine development, and clinical applications.
Esr1+ hypothalamic-habenula neurons shape aversive states
Authors: Daniela Calvigioni, Janos Fuzik, Pierre Le Merre, Marina Slashcheva, Felix Jung, Cantin Ortiz, Antonio Lentini, Veronika Csillag, Marta Graziano, Ifigeneia Nikolakopoulou, Moritz Weglage, Iakovos Lazaridis, Hoseok Kim, Irene Lenzi, Hyunsoo Park, Björn Reinius, Marie Carlén, Konstantinos Meletis
Journal: Nature Neuroscience (2023)

Excitatory projections from the lateral hypothalamic area (LHA) to the lateral habenula (LHb) drive aversive responses. We used patch-sequencing (Patch-seq) guided multimodal classification to define the structural and functional heterogeneity of the LHA-LHb pathway. Our classification identified six glutamatergic neuron types with unique electrophysiological properties, molecular profiles and projection patterns. We found that genetically defined LHA-LHb neurons signal distinct aspects of emotional or naturalistic behaviors, such as estrogen receptor 1-expressing (Esr1+) LHA-LHb neurons induce aversion, whereas neuropeptide Y-expressing (Npy+) LHA-LHb neurons control rearing behavior. Repeated optogenetic drive of Esr1+ LHA-LHb neurons induces a behaviorally persistent aversive state, and large-scale recordings showed a region-specific neural representation of the aversive signals in the prelimbic region of the prefrontal cortex. We further found that exposure to unpredictable mild shocks induced a sex-specific sensitivity to develop a stress state in female mice, which was associated with a specific shift in the intrinsic properties of bursting-type Esr1+ LHA-LHb neurons. In summary, we describe the diversity of LHA-LHb neuron types and provide evidence for the role of Esr1+ neurons in aversion and sexually dimorphic stress sensitivity.
A mitotic NADPH upsurge promotes chromosome segregation and tumour progression in aneuploid cancer cells
Authors: Aoxing Cheng, Tian Xu, Weiyi You, Ting Wang, Dongming Zhang, Huimin Guo, Haiyan Zhang, Xin Pan, Yucai Wang, Liu Liu, Kaiguang Zhang, Jue Shi, Xuebiao Yao, Jing Guo, Zhenye Yang
Journal: Nature Metabolism (2023)
Targeting Type 2 Inflammation and Epithelial Alarmins in Chronic Obstructive Pulmonary Disease: A Biologics Outlook
Authors: Klaus F. Rabe, Stephen Rennard, Fernando J. Martinez, Bartolome R. Celli, Dave Singh, Alberto Papi, Mona Bafadhel, Jigna Heble, Amr Radwan, Xavier Soler, Juby A. Jacob Nara, Yamo Deniz, Paul J. Rowe
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous, progressive inflammatory airway disease associated with significant impact on patients’ lives, including morbidity and mortality, and significant health-care related costs. Current pharmacologic strategies, including first- and second-line therapies such as long-acting β2-agonists, long-acting muscarinic antagonists, inhaled corticosteroids, phosphodiesterase 4 inhibitors, and macrolides, provide relief in patients with COPD. However, many patients remain symptomatic, with persistent symptoms and/or acute exacerbations, and progressive lung function loss. While neutrophilic inflammation is the most common type of inflammation in COPD, 20–40% of patients with COPD exhibit type 2 inflammation, with roles for CD4+ T helper type 2 cells, type 2 innate lymphoid cells, eosinophils, and alternatively activated macrophages. Based on the current limitations of available therapies, significant unmet need exists in COPD management, including the need for targeted therapies to address the underlying pathophysiology leading to disease progression, such as type 2 inflammation, as well as biomarkers to help select patients that would most benefit from the new therapies. Significant progress is being made, with our evolving understanding of the pathobiology of COPD leading to novel therapeutic targets including epithelial alarmins. In this review we describe the current therapeutic landscape in COPD, discuss unmet treatment needs, review the current knowledge of type 2 inflammation and epithelial alarmins in COPD, explore potential biomarkers of type 2 inflammation in COPD, and finally provide a rationale for incorporating therapies targeting type 2 inflammation and epithelial alarmins in COPD.
Penetrance of pathogenic genetic variants associated with premature ovarian insufficiency
Authors: Saleh Shekari, Stasa Stankovic, Eugene J Gardner, Gareth Hawkes, Katherine A Kentistou, Robin N Beaumont, Alexander Mörseburg, Andrew R Wood, Julia K Prague, Gita D Mishra, Felix R Day, Julia Baptista, Caroline F Wright, Michael N Weedon, Eva R Hoffmann, Katherine S Ruth, Ken K Ong, John R B Perry, Anna Murray
Journal: Nature Medicine (2023)
The airway microbiome mediates the interaction between environmental exposure and respiratory health in humans
Authors: Lifeng Lin, Xinzhu Yi, Haiyue Liu, Ruilin Meng, Saiqiang Li, Xiaomin Liu, Junhao Yang, Yanjun Xu, Chuan Li, Ye Wang, Ni Xiao, Huimin Li, Zuheng Liu, Zhiming Xiang, Wensheng Shu, Wei-jie Guan, Xue-yan Zheng, Jiufeng Sun, Zhang Wang
Journal: Nature Medicine (2023)
A wireless patch for the monitoring of C-reactive protein in sweat
Authors: Jiaobing Tu, Jihong Min, Yu Song, Changhao Xu, Jiahong Li, Jeff Moore, Justin Hanson, Erin Hu, Tanyalak Parimon, Ting-Yu Wang, Elham Davoodi, Tsui-Fen Chou, Peter Chen, Jeffrey J. Hsu, Harry B. Rossiter, Wei Gao
Journal: Nature Biomedical Engineering (2023)
Blood–brain barrier injury and neuroinflammation induced by SARS-CoV-2 in a lung–brain microphysiological system
Authors: Peng Wang, Lin Jin, Min Zhang, Yunsong Wu, Zilei Duan, Yaqiong Guo, Chaoming Wang, Yingqi Guo, Wenwen Chen, Zhiyi Liao, Yaqing Wang, Ren Lai, Luke P Lee, Jianhua Qin
Journal: Nature Biomedical Engineering (2023)
Childhood Cigarette Smoking and Risk of Chronic Obstructive Pulmonary Disease in Older U.S. Adults
Authors: James D. Sargent, Michael Halenar, Alexander W. Steinberg, Jenny Ozga, Zhiqun Tang, Cassandra A. Stanton, Laura M. Paulin
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

It is not certain the extent to which childhood smoking adds chronic obstructive pulmonary disease (COPD) risk independent of lifetime cigarette exposure.
AMEERA-3: Randomized Phase II Study of Amcenestrant (Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Monotherapy in Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer
Authors: Sara M. Tolaney, Arlene Chan, Katarina Petrakova, Suzette Delaloge, Mario Campone, Hiroji Iwata, Parvin F. Peddi, Peter A. Kaufman, Elisabeth De Kermadec, Qianying Liu, Patrick Cohen, Gautier Paux, Lei Wang, Nils Ternès, Eric Boitier, Seock-Ah Im
Journal: Journal of Clinical Oncology (2023)

Amcenestrant (oral selective estrogen receptor degrader) demonstrated promising safety and efficacy in earlier clinical studies for endocrine-resistant, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (aBC).
Seven-Year Follow-Up of the Phase III KEYNOTE-006 Study: Pembrolizumab Versus Ipilimumab in Advanced Melanoma
Authors: Caroline Robert, Matteo S. Carlino, Catriona McNeil, Antoni Ribas, Jean-Jacques Grob, Jacob Schachter, Marta Nyakas, Damien Kee, Teresa M. Petrella, Arnold Blaustein, Michal Lotem, Ana Arance, Adil I. Daud, Omid Hamid, James Larkin, James Anderson, Clemens Krepler, Dmitri Grebennik, Georgina V. Long
Journal: Journal of Clinical Oncology (2023)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Immune checkpoint inhibitors have led to unprecedented prolongation of overall survival (OS) for patients with advanced melanoma. Five-year follow-up of KEYNOTE-006 showed pembrolizumab prolonged survival versus ipilimumab. Efficacy results with 7-year follow-up are presented. At data cutoff (April 19, 2021), median follow-up was 85.3 months (range, 0.03-90.8 months). Median OS was 32.7 months for pembrolizumab versus 15.9 months for ipilimumab (hazard ratio [HR], 0.70; 95% CI, 0.58 to 0.83); 7-year OS was 37.8% and 25.3%, respectively. OS HRs favored pembrolizumab regardless of BRAF status or prior BRAF/MEK-inhibitor treatment and prognostic characteristics (elevated lactate dehydrogenase, large tumor size, and brain metastasis). Median modified progression-free survival (mPFS) was 9.4 months for pembrolizumab versus 3.8 months for ipilimumab; 7-year mPFS was 23.8% and 13.3%, respectively. In patients who completed ≥94 weeks of pembrolizumab, the 5-year OS was 92.9% and the 5-year mPFS was 70.1%. The objective response rate with second-course pembrolizumab (n = 16) was 56% (95% CI, 30 to 80) and the 2-year mPFS was 62.5%. These findings confirm that pembrolizumab provides long-term survival benefit in advanced melanoma.
Viral-associated Pulmonary Aspergillosis: Have We Finally Overcome the Debate of Colonization versus Infection?
Authors: Werner C. Albrich, Frédéric Lamoth
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Viral-associated Pulmonary Aspergillosis: Have We Finally Overcome the Debate of Colonization Versus Infection?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Female athlete health domains: a supplement to the International Olympic Committee consensus statement on methods for recording and reporting epidemiological data on injury and illness in sport
Authors: Isabel S Moore, Kay M Crossley, Kari Bo, Margo Mountjoy, Kathryn E Ackerman, Juliana da Silva Antero, Jorunn Sundgot Borgen, Wendy J Brown, Caroline S Bolling, Benjamin Clarsen, Wayne Derman, Paul Dijkstra, Amber Donaldson, Kirsty J Elliott-Sale, Carolyn A Emery, Lene Haakstad, Astrid Junge, Nonhlanhla S Mkumbuzi, Sophia Nimphius, Debbie Palmer, Mireille van Poppel, Jane S Thornton, Rita Tomás, Phathokuhle C Zondi, Evert Verhagen
Journal: British Journal of Sports Medicine (2023)

The IOC made recommendations for recording and reporting epidemiological data on injuries and illness in sports in 2020, but with little, if any, focus on female athletes. Therefore, the aims of this supplement to the IOC consensus statement are to (i) propose a taxonomy for categorisation of female athlete health problems across the lifespan; (ii) make recommendations for data capture to inform consistent recording and reporting of symptoms, injuries, illnesses and other health outcomes in sports injury epidemiology and (iii) make recommendations for specifications when applying the Strengthening the Reporting of Observational Studies in Epidemiology-Sport Injury and Illness Surveillance (STROBE-SIIS) to female athlete health data.In May 2021, five researchers and clinicians with expertise in sports medicine, epidemiology and female athlete health convened to form a consensus working group, which identified key themes. Twenty additional experts were invited and an iterative process involving all authors was then used to extend the IOC consensus statement, to include issues which affect female athletes.Ten domains of female health for categorising health problems according to biological, life stage or environmental factors that affect females in sport were identified: menstrual and gynaecological health; preconception and assisted reproduction; pregnancy; postpartum; menopause; breast health; pelvic floor health; breast feeding, parenting and caregiving; mental health and sport environments.This paper extends the IOC consensus statement to include 10 domains of female health, which may affect female athletes across the lifespan, from adolescence through young adulthood, to mid-age and older age. Our recommendations for data capture relating to female athlete population characteristics, and injuries, illnesses and other health consequences, will improve the quality of epidemiological studies, to inform better injury and illness prevention strategies.
Re: Timothée Olivier, Kerrington Powell, Vinay Prasad. Lutetium-177-PSMA-617 in Metastatic Castration-resistant Prostate Cancer: Limitations of the VISION Trial. Eur Urol. 2023;84:4–6
Authors: Luke C. Ardolino, Rachel Dear, Andrew J. Armstrong, Silke Gillessen, Anthony M. Joshua
Journal: European Urology (2023)
European Association of Urology Biochemical Recurrence Risk Classification as a Decision Tool for Salvage Radiotherapy—A Multicenter Study
Authors: Felix Preisser, Raisa S. Abrams-Pompe, Piter Jan Stelwagen, Dirk Böhmer, Fabio Zattoni, Alessandro Magli, Juan Gómez Rivas, Roser Vives Dilme, Matteo Sepulcri, Aritz Eguibar, Isabel Heidegger, Christoph Arnold, Christian D. Fankhauser, Felix K.-H. Chun, Henk van der Poel, Giorgio Gandaglia, Thomas Wiegel, Roderick C.N. van den Bergh, Derya Tilki
Journal: European Urology (2023)
Understanding tumour endothelial cell heterogeneity and function from single-cell omics
Authors: Qun Zeng, Mira Mousa, Aisha Shigna Nadukkandy, Lies Franssens, Halima Alnaqbi, Fatima Yousif Alshamsi, Habiba Al Safar, Peter Carmeliet
Journal: Nature reviews. Cancer (2023)